rs11546512

Variant names:

• chr5-163513993-A-G
• rs11546512
• NM_013283.5:c.525A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_013283.5(MAT2B):​c.525A>G​(p.Leu175Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,610,620 control chromosomes in the GnomAD database, including 16,808 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. L175L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.12 (1375 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15433 hom.)
• Consequence: MAT2B NM_013283.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.1225
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 9 publications found

Genes affected

MAT2B (HGNC:6905): (methionine adenosyltransferase 2 non-catalytic beta subunit) The protein encoded by this gene belongs to the methionine adenosyltransferase (MAT) family. MAT catalyzes the biosynthesis of S-adenosylmethionine from methionine and ATP. This protein is the regulatory beta subunit of MAT. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013283.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2B	NM_013283.5	MANE Select	c.525A>G	p.Leu175Leu	splice_region synonymous	Exon 4 of 7	NP_037415.1	A0A140VJP2
	MAT2B	NM_182796.2		c.492A>G	p.Leu164Leu	splice_region synonymous	Exon 4 of 7	NP_877725.1	Q9NZL9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2B	ENST00000321757.11	TSL:1 MANE Select	c.525A>G	p.Leu175Leu	splice_region synonymous	Exon 4 of 7	ENSP00000325425.6	Q9NZL9-1
	MAT2B	ENST00000280969.9	TSL:1	c.492A>G	p.Leu164Leu	splice_region synonymous	Exon 4 of 7	ENSP00000280969.5	Q9NZL9-2
	MAT2B	ENST00000518095.5	TSL:1	c.525A>G	p.Leu175Leu	splice_region synonymous	Exon 4 of 5	ENSP00000428046.1	Q9NZL9-3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18322 AN: 152134 Hom.: 1376 Cov.: 33

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.127 AC: 31701 AN: 248896 AF XY: 0.133

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.0647

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.00745

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.141 AC: 205337 AN: 1458368 Hom.: 15433 Cov.: 32 AF XY: 0.142 AC XY: 102808 AN XY: 725480

African (AFR) AF: 0.0538 AC: 1794 AN: 33340

American (AMR) AF: 0.0676 AC: 2984 AN: 44136

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2871 AN: 26006

East Asian (EAS) AF: 0.0155 AC: 615 AN: 39552

South Asian (SAS) AF: 0.138 AC: 11819 AN: 85662

European-Finnish (FIN) AF: 0.214 AC: 11406 AN: 53296

Middle Eastern (MID) AF: 0.129 AC: 741 AN: 5746

European-Non Finnish (NFE) AF: 0.149 AC: 165191 AN: 1110378

Other (OTH) AF: 0.131 AC: 7916 AN: 60252

GnomAD4 genome AF: 0.120 AC: 18321 AN: 152252 Hom.: 1375 Cov.: 33 AF XY: 0.122 AC XY: 9111 AN XY: 74430

African (AFR) AF: 0.0573 AC: 2383 AN: 41576

American (AMR) AF: 0.101 AC: 1547 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3462

East Asian (EAS) AF: 0.0123 AC: 64 AN: 5194

South Asian (SAS) AF: 0.135 AC: 651 AN: 4830

European-Finnish (FIN) AF: 0.213 AC: 2250 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10579 AN: 67994

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.137 Hom.: 2055

Bravo AF: 0.106

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		1.3
Mutation Taster		=63/37	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.27
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11546512; hg19: chr5-162940999; COSMIC: COSV55200836; COSMIC: COSV55200836;